Multiple core structure libraries

The Use of Templates in Combinatorial Chemistry for the Solid-Phase Synthesis of Multiple Core Structure Libraries... 

By explaining these templates in detail, we will show their possibilities as key intermediates for the synthesis of a large range of different core structures. Tempest and Armstrong [11] have introduced the term Multiple Core Structure Libraries (MCSL) for resin-bound squaric acid derivatives. 

Several other promising templates suitable for the synthesis of multiple core structure libraries have been reported, but their synthetic potential has not yet been fully investigated. 

As a consequence of the progress and success of diverse oligomer libraries, experts in combinatorial synthetic oligomers, glycopeptide and oligosaccharide libraries, RNA-and DNA-aptamers have each contributed their news in these fields, while novel experimental examples of the use of templates in combinatorial chemistry for the solid-phase synthesis of multiple core structure libraries provide some insight to praxis-relevant work. 

P.A. Tempest, R.W. Armstrong, Cyclobutenedione derivatives on solid support toward multiple core structure libraries, J. Am. Chem. Soc. 1997, 119, 7607-7608. 

Developing synthetic routes that provide skeletal diversity with multiple core scaffolds or backbone structures is an area of particular current interest. Several approaches to generating such multiscaffold libraries have been advanced. In one straightforward strategy, Schultz synthesized a 45 140-member library from multiple heterocyclic scaffolds, each having a set of functional groups in common [39]. The scaffolds were coupled as building blocks, which were then... 

A number of examples such as 1,3-dioxanes, macrolactones, °° ring-containing biaryls, ° spirooxindoles, alkaloid-like compounds, and polycyclic compounds from the Schreiber group illustrate this approach to natural product-like libraries (see Chapter 11). An early example converted shikimic acid into intermediate tetracyclic y-butyrolactones, which were then functionalized around the core structure (see Chapter 11, Subsection 11.10.2). y-Butyrolactones, found in about 10% of all natural products and which exhibit a broad range of biological activities, are a key element in a number of recent natural product-like compounds. A more recent example, inspired by the rich skeletal diversity of indole alkaloids, utilized the rhodium(II)-catalyzed consecutive cyclization-cycloaddition reactions developed by Padwa and coworkers (Scheme 1.4). A stereocontrolled tandem reaction utilizing the versatile scaffold allowed for multiple modes of intramolecular reactions. 

We next explored the applications of liquid-phase synthesis of benzofused heterocycles from a common building block PEG-bound nitro-activated aryl fluoride (Fig. 8). In these synthetic strategies, we created multiple accesses to the structurally diverse core molecules based on a fundamental scaffold 10. We focused on the construction of a variety of benzimidazole libraries starting from a versatile synthon 4-fluoro-3-nitrobenzoic acid via liquid-phase nucleo-... 

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